RESEARCH ARTICLE Open Access

Shortcomings and missed potentials in themanagement of migraine patients -experiences from a specialized tertiary carecenterChristian Ziegeler1, Greta Brauns1, Tim P. Jürgens1,2 and Arne May1*

Abstract

Background: Migraine is a common and severely disabling neurological disorder affecting millions of patients inEurope. Despite the availability of evidence-based national and international guidelines, the management ofmigraine patients often remains poor, which is often attributed to a low availability of headache specialists. The aimof this study was to investigate the adherence to national guidelines and to assess the possible potential ofoptimized therapy regimens in migraine patients.

Methods: We collected data of migraine patients presenting to our out-patient clinic via standardizedquestionnaires regarding headache, diagnostics and experience with previous treatments. We also assessed theefficacy of treatment started by our center.

Results: 1,935 migraine patients were included between 2010 and 2018. In the 12 months before consulting ourheadache clinic 89.5% of the patients had consulted a general practitioner and 74.9% had consulted a neurologistbecause of their migraine. Nevertheless, 50% of the patients underwent unnecessary diagnostics and 34.2% had notbeen treated according to evidence-based treatment guidelines. Out of 1,031 patients who had not beenprescribed a preventative treatment 627 (60.8%) had in average 3 or more migraine attacks per month and thusqualified for a preventative treatment. These patients missed in the 3 months prior to consultation on average 5work or school days. Initiating a preventative treatment was effective in 71.2% of the patients, that provided follow-up data.

Conclusions: Our data suggest, that many migraine patients to this day do not receive state-of-the-art therapy.Adherence to national and international European guidelines could improve the outcome in migraine patients.Future research should try to answer why guidelines are not followed.

Keywords: Migraine, Care, Management, Guideline

IntroductionMigraine is a common and severely disabling neuro-logical disorder affecting millions of patients [1] and dueto its high prevalence it is considered to be one of themost disabling diseases worldwide [2]. The prevalence inEurope is estimated to be around 15% [3]. Even thoughcosts-per-subject are not as high as in other neurological

and central nervous system diseases, the combined dir-ect and indirect annual costs of migraine in theEuropean Union accounted for €111 billion in a 2011study [4].Despite the availability of evidence-based national [5]

and international [6] guidelines, the management andcare provided to migraine patients is far from ideal [7].Migraine patients still experience significant time delaysin the diagnosis of their headache disorder [8] and themajority of migraine patients seem to not receive ad-equate acute [7] and preventative treatment [9]. In this

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made.

* Correspondence: a.may@uke.de1Department of Systems Neuroscience, University Medical CenterHamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, GermanyFull list of author information is available at the end of the article

The Journal of Headache and Pain

Ziegeler et al. The Journal of Headache and Pain (2019) 20:86 https://doi.org/10.1186/s10194-019-1034-8

context it has been suggested that the diagnosis of mi-graine and its implications are still not fully recognizedby the patient and especially by the medical community[10]. However, patients referred to a 3rd referee center(tertiary care center) such as University headache out-patient clinic are usually already diagnosed and treatedby general practitioners and neurologists and shouldtherefore represent a group of patients who are particu-larly hard to treat. Since the headache syndromes ofthese patients are per definition recognized by the pa-tient and by the medical community, the question ariseswhether these patients were treated correctly or not, i.e.whether these patients suffer from particularly severeheadache disorders and therefore are medically intract-able or whether they have not been treated properly des-pite recognition of the disease. The aim of the currentstudy is therefore to investigate the adherence to na-tional migraine guidelines for diagnosis and medicaltreatment in a sample of nearly 2000 patients consultinga third referee center for headache.

MethodsThis study was approved by the local ethics committeeof the chamber of physicians of Hamburg, Germany (PV3185) and patients gave written informed consent ac-cording to the Declaration of Helsinki.The headache and facial pain outpatient clinic is a spe-

cialized tertiary care center within the University Med-ical Center Hamburg-Eppendorf with approximately1000 to 1200 annual registered patient contacts. Thesecontacts reflect all combined consultations by migrainepatients, patients with other primary or secondary head-aches as well as patients suffering from primary and sec-ondary facial pain syndromes. It must be noted, thatmultiple personal contacts (even for prescriptions) bythe same patient are respectively counted as additionalcontacts due to the nature of German reimbursementpolicy. Due to German data protection law, data frompatients not willing to participate in this study was notsaved and we are therefore not able to provide acomplete overview over all patients who consulted us.Our outpatient clinic is specifically designed to be con-

sulted by patients in whom the general practitioner or otherexperts such as neurologists ask for a second opinion or atherapy optimization, however also self-referrals by patientsare possible and not separately counted. We usually recom-mend adjusting therapies in accordance to the nationalGerman guideline for the acute and preventative treatmentof migraine, with a focus on implementing pharmacologicaland non-pharmacological treatment regimens [5].Before the first consultation, patients are asked to vol-

untarily fill out a custom-built electronic questionnaire(AC-STB, http://www.ac-stb.de/de/) to provide personalsociodemographic data, description of disease specific

symptomatology, health care utilization, as well as otherstandardized questionnaires such as the MIDAS [11].Medical records of the consultation and a questionnairefilled out by the clinicians are linked to the data. Dataare stored pseudonymized and for the evaluation of thisstudy they were anonymized.Clinicians focus on additional disease characteristics

and especially previous treatment strategies, including de-scription and evaluation of the pharmacological treatment.The combination of these questionnaires allows for com-prehensive and multi-dimensional data acquisition.Only correctly and duly completed data sets by all

patients willing to participate are included into thedatabase. Exclusion criteria were patients refusal toparticipate in the questionnaire and patients not fit-ting ICHD-3 criteria [12] for migraine.Consecutive consultations are also documented with a

questionnaire designed to document adherence to med-ical advice and treatment as well as efficacy and toler-ability of such treatments. Headache days are usuallyevaluated calendar-based, but some patients refrain fromusing a calendar. In these cases, we rely on the patients’oral information.Since migraine comprises the largest group of patients,

providing meaningful data, we focused on migraine ac-cording to ICHD-3 criteria [12] in the following. Ofnote, for all our parameters that we report we focusedon the first contact with the patients to get a clear pic-ture what type of patients consult a university outpatientspecialist clinic. Only regarding preventative efficacy ofmedications we prescribed, we looked into follow-upvisits. Original data are from 1935 distinct patients.

ResultsBetween the years 2010 and 2018 1,935 migrainepatients provided complete data sets. This corre-sponds to a rate of approximately 75% of all distinctmigraine patients (including possible and atypicalcases, hence the uncertainty) seen during this timeinterval. Of these 1,578 (81.6%) were female, and 357patients (18.4%) were male. The mean age at the firstconsultation was 37.3 ± 13.3 (SD) years (unknown dateof birth in two female patients).

Headache daysMigraine patients suffered 12.1 ± 9.6 headache daysper month (n = 1,879 patients, inconclusive data for56 patients). We further divided our patients intosubgroups (Table 1) of:

(i) 1–3 headache days/month(ii) 4–14 headache days/month(iii)chronic with 15 or more headache days/month

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as well as:

(iv)≥3 attacks/month and(v) < 3 attacks/month

In chronic migraine patients, migraine and headachedays were not separated for this analysis.

Medication overuseAt the time of the first consultation 9.2% (179/1,935) ofall patients fulfilled the ICHD-3 criteria of medication-overuse headache. Of these, 77.1% (138/179; not speci-fied: 2) had never undertaken a withdrawal.In total, a withdrawal from headache medication had

been undertaken by 11.8% of all patients (229/1,925 pa-tients, not specified: 10) prior to the first consultation.

Of those 38.0% were hospitalized and 59.0% underwentwithdrawal as outpatients (222; not specified: 7). Theselifetime data combine self-initiated withdrawals, as wellas withdrawals suggested by doctors.

Health care utilizationPatients had an average of 7.2 ± 10.0 outpatient consulta-tions because of their migraine in the last 12months be-fore the initial consultation (n = 1,927, n = 8 missing data).Most of the patients had consulted a general practitioner(89.5%) followed by neurologists (74.9%) and orthopedists(47.4%) (see Fig. 1).Throughout their lifetime, 54.2% (1,048/1,935) of the

patients underwent a computer tomography (CCT)because of their headache and 51.4% (n = 995/1,935) re-ceived an MRI of the head, none of which changed thediagnosis.

Table 1 All migraine patients grouped by sex, amount of migraine days, number of attacks and previous preventative treatments intheir lifetime, overall (n = 1,935). n/a: not applicable

Group Overall (n = 1935) Female (n = 1578) Male (n = 357)

(i) 1-3 days 367 (19.0%) 286 (18.1%) 81 (22.7%)

(ii) 4-14 days 949 (49.0%) 790 (50.1%) 159 (44.5%)

(iii) chronic(15 days or more)

563 (29.1%) 451 (28.6%) 112 (31.4%)

n/a 56 (2.9%) 51 (3.2%) 5 (1.4%)

At least one preventative treatment No prior preventative treatment

overall 904/1935 (46.7%) 1031/1935 (53.3%)

(iv) ≥3 attacks 672 (74.3%) 627 (60.8%)

(v) <3 attacks 209 (23.1%) 371 (36.0%)

n/a 23 (2.5%) 33 (3.2%)

Fig. 1 Specialists which were consulted by patients because of their migraine (GP: general practitioner; NEURO: neurologist; ORTH: orthopedist,OPHTH: ophthalmologist, DENT: dentist, ACU: acupuncture specialist, GYN: gynecologist, OTOL: otolaryngologist, PSYCHO: psychologist, NATUR:natural medicine, HOMEO: homeopath, PAIN: pain specialist, INT: internist, PSYCHIA: psychiatrist, CHIN: traditional Chinese medicine specialist,NEUROS: neurosurgeon, MIRACL: faith healer, RHEUM: rheumatologist (multiple answers possible). (n = 1,935)

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Nearly one third of all patients reported to have atleast once presented to an emergency department be-cause of migraine (31.3%, n = 605/1,935) and these pa-tients had presented themselves in average 4.1 ± 7.4times in total. In-patient stays were also common: 22.5%(n = 435/1,935) of patients had previously been hospital-ized due to migraine headaches (2.9 ± 5.8 in-patienttreatments in these patients in average).

Previous preventative treatmentAn important, effective and often overlooked aspect ofthe preventative treatment of migraine are non-pharmacological [13] strategies, including enduranceand relaxation training as well as biofeedback, lifestylemodifications and possibly specialized cognitive behaviortherapy as listed by the German migraine treatmentguideline [5]. For this study however, we focus onpharmacological interventions.The first line pharmacological preventative treatments

proposed by the German guideline for the treatment ofmigraine are beta blockers (metoprolol, propranolol),calcium channel blockers (flunarizine), anticonvulsants(topiramate, valproate) and tricyclic antidepressants(amitriptyline). A preventative is considered necessarywhen the patient suffers more than 3 migraine attacksper months which affect the quality of life, when attacksconsistently last longer than 72 h or do not respond toacute treatment [5].More than one third of the patients (34.2%, n = 661/1,

935) have not been treated according to the Ger-man guideline for the treatment of migraine. Only 0.6%of our patients (11/1,935) had tried all recommendedguideline treatment strategies and were therefore consid-ered medically intractable.More than half of the patients (53.3%, n = 1,031/1,935)

had either never been prescribed a preventative treat-ment or, if described, have not taken it (Table 1). 60.8%(627/1,031) of these patients had in average 3 or moremigraine attacks per month (Table 1) and thus qualifiedfor a preventative treatment. Only 36.0% (371/1,031) ofthe patients with no prior preventative treatment had inaverage less than 3 migraine attacks per month (incon-clusive data for 3.2% [33/1,031]) (Table 1). Patients withno prior preventative treatment missed in the 3 monthsprior to their first consultation on average 5.1 ± 10.9(SD) work or school days (MIDAS, Item 1), could notdo household work on 8.2 ± 11.1 days (MIDAS, Item 3)and missed on an average of 7.3 ± 11.0 days family orleisure activities (MIDAS, Item 5) because of their mi-graine headaches.Patients with no prior preventative treatment and

more than 3 migraine attacks per month had consulted agenral practitioner in 87.9% (551/627) of the casesand aneurologist in 67.5% (423/627) of the cases.

Of 904 patients who used preventative medicationsprior to their consultation, 45.8% had one, 21.2% had twoand 10.3% reported three unsuccessful treatment at-tempts. Successful treatments were reported by 22.5%(203/904) of the patients with one, 3.9% (35/904) with twoand 0.8% with three preventatives. Success was definedthat a given preventative treatment reduced the headachefrequency by at least by 50% and was well tolerated. Theclinicians documented unsuccessful treatments when themedication was ineffective or not well tolerated.

Potential of preventative medication when used followingguideline therapyOne third of the patients consulted us for at least onemore time (33.4%, 647/1,935). 17.9% (346/1,935) wereseen twice, and 10.7% (207/1,935) of patients consultedus three or more times after the first consultation. Forthese consultations the evaluation of the overall therapysuccess as well as the success of the acute and preventa-tive pharmacological treatments were assessed. In mostcases the second consultation took place between 3 and6months after the first consultation.Figure 2 shows evaluation of 647 patients that consulted

the out-patient clinic for a second time. Usually these pa-tients were highly affected by their migraine headachesand previous preventative treatment had been unsuccess-ful or never tried. Efficacy and tolerability were retrospect-ively rated in an ordinal rating scale by the clinicians withthe possible answers ‘very good’, ‘good’, ‘rather good’, ‘ratherbad’, ‘bad’, ‘very bad’. The overall success of the therapy ini-tiated in our outpatient clinic was evaluated as very goodor good in 71.2% of the cases. Acute treatment showed avery good or good efficacy in 77.3% of the cases and aneven better tolerability. The preventative treatment wasfor the most part effective (59.5% either ‘very good’, ‘good’,or ‘rather good’) and well tolerated (58.7% either ‘verygood’, ‘good’, or ‘rather good’).The efficacy and tolerability rates for each of the four

most often prescribed first-line preventative drugs topir-amate, flunarizine, beta-blockers and amitriptyline areshown in Fig. 3. The results of all substances for efficacyand tolerability are comparable, however there is a trendtowards more side effects of amitriptyline compared tothe other three.Overall, we have data for 190 follow-up patients who

previously had not been prescribed a preventative treat-ment even though they had more than 3 attacks permonth. Figure 4 shows the efficacy and tolerability ratesfor 140 out of these patients, in whom a preventativetreatment had been prescribed and tried (the other 50 pa-tients did not want to try a preventative for different rea-sons). The efficacy of preventative treatments in thesepatients was ‘very good’, good’ or ‘rather good’ in 79.3% of

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Fig. 3 Efficacy and tolerability of the four first-line preventative migraine medications as evaluated by the clinicians during the second consultation(3–6months after first consultation). TOP: topiramate, FLU: flunarizine, BETA: beta blockers, TCA: tricyclic antidepressants. (n = 647). n/a: not applicable

Fig. 2 Therapy evaluation of migraine patients presenting for a second time to the out-patient clinic. Clinicians’ evaluation of overall success aswell as evaluation of acute and preventative treatment regarding efficacy and tolerability. (n = 647). n/a: not applicable

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the cases, the tolerability was similar with 75.8% of thecases being ‘very good’, ‘good’ or ‘rather good’ (Fig. 4).

DiscussionOur data suggest that to this day a significant percentageof migraine patients might not be introduced to state-of-the-art pharmacological therapy as lined out in nationalguidelines. Given that most patients improve clinically,when we treated pharmacologically according to guide-lines, the low adherence to evidence-based treatmentstrategies has considerable, and more importantly, avoid-able personal as well as socio-economic consequences. Itis possible that the majority of migraine patients istreated well by their GP and other specialists and thatthe small percentage of patients presenting to a special-ized headache center is not representative for all mi-graine patients. This possibility is worth considering,however not only our personal experience and this data,but also previous studies strongly indicate, that there areunmet needs for migraine patients [7].The German Migraine and Headache Society (DMKG)

has been founded in 1979 with the aim to foster researchand treatment in headache. Since then they publish regu-lar and updated evidence based treatment guidelines [5].Additionally, in partnership with the German Neuro-logical Society (DGN) there are updates and refreshers onthe treatment of migraine patients implemented into na-tional and international conferences and meetings as wellas innumerable regional smaller seminars. Moreover, alltreatment guidelines are freely available to all readers, notrestricted to doctors, in the internet (www.dmkg.de). Des-pite this abundant supply of knowledge, migraine patientssee several doctors and specialists because of their

headaches, undergo diagnostic procedures including CTand MR-imaging which are mostly not indicated [14] andare not treated properly. Of note, we only report patientswho consulted the headache clinic of the HamburgUniversity Medical Center and one could argue thatpatients who have been treated properly escape us, thusoverestimating the negative results. This study is not pow-ered or designed to reflect the amount of patients who aretreated properly by primary or secondary care specialists,however as mentioned the experience of many headachespecialists and literature suggests that many migraine pa-tients are treated poorly [7].It is striking that we found the prior treatment as not in

line with the official guidelines in over a third of all pa-tients. This problem of sub-optimal adherence to nationalguidelines in headache has been discussed before [15].Also, half of the patients, presenting to a specialized ter-tiary care headache clinic, had never been prescribed apreventative treatment. The data shows that over 60% ofthese patients should have received a preventative treat-ment (Table 1) and additionally indicates that many ofthese patients potentially profit from it (Fig. 4).A limitation of our study approach is that we cannot

provide follow up data for all patients and therefore we ac-knowledge that especially the effect of the preventativetreatments proposed by us has to be viewed critically. Thisstudy reflects the clinical reality of treating migraine pa-tients in a tertiary care setting. Patients are offered topresent themselves again in case they do not profit fromthe recommended therapy. Many patients especially withpositive outcomes however do not consult us again butare subsequently treated by their primary care physiciansagain. There are patients who only consulted us once,

Fig. 4 Efficacy and tolerability of preventative treatments in general in patients that had more than 3 attacks per month but had previously notbeen prescribed a preventative migraine treatment. (n = 140)

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which were probably inadequately treated or suffer side-effects and are therefore lost for follow-up. However, therate of patients who cancel a consultation is with 10% ofpatients remarkably stable since years (data collected on amonthly basis), despite a more than 90% rate of all pa-tients who would recommend and consult us again (datacollected 4 weeks after consultation by phone). Still, it ispossible that we overestimate the success rate of the pre-ventative treatment initiated by us to a certain extent andwe acknowledge this fact. The rates of the improved out-come in patients that had previously not been prescribeda preventative treatment should therefore be seen as anindication that adherence to guideline therapy possiblyimproves the outcome, as expected.At the same time, although unlikely, we cannot rule out

that we overestimate the adherence to guidelines sincesome patients may have, for example, a beta blockerintended for the treatment of hypertension or amitriptylineintended for the treatment of depression and we docu-mented it as under the migraine indication. We also notethat clinical experience and also recent studies show thatthe adherence to oral preventative medication, especially inchronic migraine is low [16]. This is most likely owed to in-sufficient success combined with problematic side effects.In conclusion, this study shows the importance to better

implement treatment guidelines into day-to-day clinicalpractice. Additionally, headache education should play alarger role in medical school for young doctors. It is theauthors’ experience in teaching headache to students, thatdespite its relevance, headache only plays a minor role inthe curricula. This also holds true internationally [17],however useful curricula have been proposed [18]. Weknow that inadequate acute treatment leads to migrainechronification [19] and this certainly also holds true for in-sufficient preventative treatment [20]. While it is under-standable that highly consulted specialists underlie timeconstraints, it is not easily explainable why many patientswho qualify for preventative treatment have not been pre-scribed one. Given the statutory health insurance fundcosts for consultations, diagnostics and treatments it is ra-ther alarming that a considerable amount of these costs(specialist consultations, emergency admittance, MR andCCT imaging, OTC medications, non-pharmacologicaltreatment attempts etc.) are either not necessary or mayeven be contra-productive. We lack information about thedecision processes made by primary-care physicians withregard to the treatment of migraine. Many of these pa-tients, especially with episodic migraine, profit greatlyfrom first line preventative drugs. Further research shouldtry to highlight, why the adherence to guidelines in dailyclinical practice is low. Possible factors could be that clini-cians are unaware of the applicable guidelines, but alsothat medications are not well tolerated by patients andtherefore discontinued.

AcknowledgementsThe authors thank Olesja Frick, Ines Garcia-May, Laura Helene Schulte andJan Hoffmann for helping with data acquisition.

Authors’ contributionsThere are no conflicts of interests and all authors have seen and agreed withthe manuscript. CZ: data acquisition, analysis and interpretation, drafting andwriting of the manuscript. GB: Data acquisition and analysis. TJ: Studyconcept and design, data acquisition. AM: Study concept and design, dataacquisition, data analysis and interpretation, drafting and writing of themanuscript, study supervision. All authors read and approved the finalmanuscript.

FundingThis study was funded in part by an unrestricted scientific grant fromNovartis to the UKE. The funding source did not influence study design,conduction, interpretation or writing in any way.

Availability of data and materialsAll patients who participated in this study gave written informed consent.However, this consent did not include a provision stating that individual rawdata can be made freely accessible to the public. Therefore, in accordancewith the German data protection act §4 the underlying raw data cannot bemade accessible to the public. Researchers meeting the criteria for access toconfidential data may access anonymized data upon request, involving thedocumentation of data access.

Ethics approval and consent to participateThis study was approved by the local ethics committee of the chamber ofphysicians of Hamburg, Germany (PV 3185) and patients gave writteninformed consent according to the Declaration of Helsinki.

Competing interestsNone regarding the content of this paper.CZ received speaker honoraria and from Novartis, Teva, Allergan and Lillyand received consulting fees from Novartis and Teva.TPJ received honoraria and consulting fees from Autonomic Technologies,Inc., Allergan, Lilly, Novartis and TEVA. He also received travel grants fromAllergan.GB and AM report no competing interests.

Author details1Department of Systems Neuroscience, University Medical CenterHamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany. 2Departmentof Neurology, University Medical Center Rostock, Rostock, Germany.

Received: 19 June 2019 Accepted: 23 July 2019

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